{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T19:04:21Z","timestamp":1792695861708,"version":"4.5.0"},"posted":{"date-parts":[[2025,12,4]]},"group-title":"Neurology","reference-count":29,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,12,4]],"date-time":"2025-12-04T00:00:00Z","timestamp":1764806400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,12,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Alzheimer\u2019s disease and related dementias (ADRD) are multifactorial disorders driven by genetic, vascular, inflammatory, lifestyle, and biological factors interacting over decades, requiring population-level analyses. However, utilizing multimodal datasets is labor-intensive, impeding discovery and equity. Multi-agentic AI systems promise workflow automation but lack ADRD-specific adaptations.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>We created a modular AI system with agents for data preparation, planning, analysis, critique, and summarization. Using data from the National Alzheimer\u2019s Coordinating Center (NACC) (n=48,876), we tested 100 literature-derived ADRD hypotheses, subsampled cohorts (100\u201310,000 participants), and 100 non-ADRD controls via iterative loops.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>The system verified 42.0\u00b12.8 hypotheses by rejecting the null, found no evidence for 16.6\u00b11.1, and deemed 41.4\u00b12.3 not testable, with consistency in negated versions. Verification rates rose from 10.4 (n=100) to 35.4 (n=10,000); controls showed 85.2\u00b10.6 non-testable.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Our system illustrates a powerful paradigm in which AI can facilitate automated data analysis, expediting advancements in population-level dementia investigations.<\/jats:p>\n                <\/jats:sec>","DOI":"10.64898\/2025.12.02.25341517","type":"posted-content","created":{"date-parts":[[2025,12,9]],"date-time":"2025-12-09T11:08:46Z","timestamp":1765278526000},"source":"Crossref","is-referenced-by-count":1,"title":["Agentic AI for automated hypothesis testing in Alzheimer\u2019s disease and related dementias"],"prefix":"10.64898","author":[{"given":"Ketan S.","family":"Saichandran","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karim","family":"Elzokm","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Osman B.","family":"Guney","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5312-8644","authenticated-orcid":false,"given":"Vijaya B.","family":"Kolachalama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2025120903084214000_2025.12.02.25341517v1.1","doi-asserted-by":"publisher","DOI":"10.1002\/alz.70235"},{"key":"2025120903084214000_2025.12.02.25341517v1.2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e3181cb3e25"},{"key":"2025120903084214000_2025.12.02.25341517v1.3","doi-asserted-by":"publisher","DOI":"10.1097\/WAD.0b013e318142774e"},{"issue":"4","key":"2025120903084214000_2025.12.02.25341517v1.4","first-page":"270","article-title":"The National Alzheimer\u2019s Coordinating Center (NACC) Database: an Alzheimer disease database","volume":"18","author":"Centers NI-AsD","year":"2004","journal-title":"Alzheimer Dis Assoc Disord"},{"key":"2025120903084214000_2025.12.02.25341517v1.5","doi-asserted-by":"publisher","DOI":"10.1002\/alz.13765"},{"key":"2025120903084214000_2025.12.02.25341517v1.6","doi-asserted-by":"publisher","DOI":"10.1002\/alz.14290"},{"key":"2025120903084214000_2025.12.02.25341517v1.7","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2018.09.009"},{"key":"2025120903084214000_2025.12.02.25341517v1.8","doi-asserted-by":"publisher","DOI":"10.1002\/dad2.12615"},{"key":"2025120903084214000_2025.12.02.25341517v1.9","doi-asserted-by":"publisher","DOI":"10.1002\/bsa3.70033"},{"key":"2025120903084214000_2025.12.02.25341517v1.10","doi-asserted-by":"publisher","DOI":"10.1002\/alz.70883"},{"key":"2025120903084214000_2025.12.02.25341517v1.11","doi-asserted-by":"publisher","DOI":"10.1038\/s41398-022-01899-w"},{"key":"2025120903084214000_2025.12.02.25341517v1.12","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-025-62590-4"},{"key":"2025120903084214000_2025.12.02.25341517v1.13","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-024-03118-z"},{"key":"2025120903084214000_2025.12.02.25341517v1.14","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-31037-5"},{"key":"2025120903084214000_2025.12.02.25341517v1.15","doi-asserted-by":"publisher","DOI":"10.1002\/alz.70255"},{"key":"2025120903084214000_2025.12.02.25341517v1.16","doi-asserted-by":"publisher","DOI":"10.1002\/alz.13509"},{"key":"2025120903084214000_2025.12.02.25341517v1.17","doi-asserted-by":"publisher","DOI":"10.1002\/alz.70278"},{"key":"2025120903084214000_2025.12.02.25341517v1.18","doi-asserted-by":"publisher","DOI":"10.1038\/sdata.2016.44"},{"key":"2025120903084214000_2025.12.02.25341517v1.19","doi-asserted-by":"publisher","DOI":"10.1038\/sdata.2016.18"},{"key":"2025120903084214000_2025.12.02.25341517v1.20","doi-asserted-by":"publisher","DOI":"10.1016\/j.media.2024.103207"},{"key":"2025120903084214000_2025.12.02.25341517v1.21","doi-asserted-by":"publisher","DOI":"10.1016\/j.media.2020.101765"},{"key":"2025120903084214000_2025.12.02.25341517v1.22","doi-asserted-by":"publisher","DOI":"10.1002\/adma.202413523"},{"key":"2025120903084214000_2025.12.02.25341517v1.23","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2024.09.022"},{"key":"2025120903084214000_2025.12.02.25341517v1.24","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgph.0004383"},{"key":"2025120903084214000_2025.12.02.25341517v1.25","doi-asserted-by":"publisher","DOI":"10.1097\/WAD.0b013e318191c7dd"},{"key":"2025120903084214000_2025.12.02.25341517v1.26","doi-asserted-by":"publisher","DOI":"10.1136\/bmjebm-2025-113913"},{"key":"2025120903084214000_2025.12.02.25341517v1.27","doi-asserted-by":"publisher","DOI":"10.1093\/gerona\/glv038"},{"key":"2025120903084214000_2025.12.02.25341517v1.28","doi-asserted-by":"publisher","DOI":"10.1007\/s10654-017-0225-3"},{"key":"2025120903084214000_2025.12.02.25341517v1.29","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-230181"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.64898\/2025.12.02.25341517","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,9]],"date-time":"2025-12-09T11:08:47Z","timestamp":1765278527000},"score":1,"resource":{"primary":{"URL":"http:\/\/medrxiv.org\/lookup\/doi\/10.64898\/2025.12.02.25341517"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,4]]},"references-count":29,"URL":"https:\/\/doi.org\/10.64898\/2025.12.02.25341517","relation":{},"subject":[],"published":{"date-parts":[[2025,12,4]]},"subtype":"preprint"}}